tbuckley/cabot-search huggingface dataset:
Updated efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic <i>NTRK</i> fusion-positive (fp) non-small cell lung cancer (NSCLC).
Authors: Byoung Chul Cho, Chao-Hua Chiu, Erminia Massarelli, Gary L Buchschacher, Koichi Goto, Tobias R. Overbeck, Herbert H. F. Loong, Cheng E. Chee, Pilar Garrido, Sebastian Heinzmann, Walter Bordogna, Harald Zeuner, Stuart Osborne, Tom John
Journal: Journal of Clinical Oncology (2023)

9047 Background: NTRK fusions, encoding for constitutively active oncogenic tropomyosin receptor kinase proteins, are present in many solid tumors, including NSCLC. As central nervous system (CNS) metastases are common in pts with advanced NSCLC, treatments with intracranial efficacy are needed. Entrectinib, a potent CNS-active tyrosine kinase inhibitor, has previously demonstrated efficacy in pts with NTRK-fp NSCLC in an integrated analysis of three phase I/II trials (ALKA-372-001 [EudraCT, 2012-000148–88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]); objective response rate (ORR) was 63.6% (14/22; data cutoff: August 31 2020). We present updated data for this cohort. Methods: Pts ≥18 years old with locally advanced/metastatic NTRK-fp tumors were enrolled and received 600 mg oral entrectinib until disease progression, toxicity, or death. At Week 4 and then every 8 weeks, tumour response was assessed by blinded independent central review (BICR) per RECIST v1.1. Co-primary endpoints were ORR and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial efficacy, and safety. Enrolment cutoff: July 2 2020; data cutoff: August 2 2021. Results: The efficacy-evaluable population included 31 pts with NTRK-fp NSCLC. Median age was 60.0 years (range 22–88); 26 pts (83.9%) had adenocarcinoma; 11 pts (35.5%) had ≥2 prior lines of systemic therapy; 18 pts (58.1%) were current or former smokers; 15 pts (48.4%) had investigator-assessed baseline CNS metastases. Median survival follow up was 21.8 months (95% CI 19.5–30.2). Entrectinib treatment showed efficacy in pts with NTRK-fp NSCLC, including those with baseline CNS metastases by investigator (Table). In pts with BICR-assessed CNS metastases, intracranial ORR was 60.0% (6/10; 95% CI 26.2–87.8), median intracranial DoR was not estimable (NE), and median intracranial PFS was 8.9 months (95% CI 5.6–NE). In the safety-evaluable population (N=35), most treatment-related adverse events (TRAEs) were Grade 1–2 and non-serious. TRAEs led to dose reduction, interruption and discontinuation in 31.4%, 28.6%, and 5.7% of pts, respectively, and no treatment-related deaths occurred. Conclusions: In line with previously reported data, treatment with entrectinib was associated with deep and durable systemic and intracranial responses in pts with advanced NTRK-fp NSCLC. Clinical trial information: EUCTR 2012-000148-88 , NCT02097810 , NCT02568267 . [Table: see text]
Healing of acute anterior cruciate ligament rupture on MRI and outcomes following non-surgical management with the Cross Bracing Protocol
Authors: Stephanie R Filbay, Matthew Dowsett, Mohammad Chaker Jomaa, Jane Rooney, Rohan Sabharwal, Phil Lucas, Andrew Van Den Heever, James Kazaglis, Justin Merlino, Mick Moran, Maggie Allwright, Donald E K Kuah, Ra Durie, Greg Roger, Mervyn Cross, Tom Cross
Journal: British Journal of Sports Medicine (2023)

Investigate MRI evidence of anterior cruciate ligament (ACL) healing, patient-reported outcomes and knee laxity in patients with acute ACL rupture managed non-surgically with the Cross Bracing Protocol (CBP).Eighty consecutive patients within 4 weeks of ACL rupture were managed with CBP (knee immobilisation at 90° flexion in brace for 4 weeks, followed by progressive increases in range-of-motion until brace removal at 12 weeks, and physiotherapist-supervised goal-oriented rehabilitation). MRIs (3 months and 6 months) were graded using the ACL OsteoArthritis Score (ACLOAS) by three radiologists. Mann-Whitney U tests compared Lysholm Scale and ACL quality of life (ACLQOL) scores evaluated at median (IQR) of 12 months (7-16 months) post-injury, and χ2 tests compared knee laxity (3-month Lachman's test and 6-month Pivot-shift test), and return-to-sport at 12 months between groups (ACLOAS grades 0-1 (continuous±thickened ligament and/or high intraligamentous signal) versus ACLOAS grades 2-3 (continuous but thinned/elongated or complete discontinuity)).Participants were aged 26±10 years at injury, 39% were female, 49% had concomitant meniscal injury. At 3 months, 90% (n=72) had evidence of ACL healing (ACLOAS grade 1: 50%; grade 2: 40%; grade 3: 10%). Participants with ACLOAS grade 1 reported better Lysholm Scale (median (IQR): 98 (94-100) vs 94 (85-100)) and ACLQOL (89 (76-96) vs 70 (64-82)) scores, compared with ACLOAS grades 2-3. More participants with ACLOAS grade 1 had normal 3-month knee laxity (100% vs 40%) and returned to pre-injury sport (92% vs 64%), compared with participants with an ACLOAS grades 2-3. Eleven patients (14%) re-injured their ACL.After management of acute ACL rupture with the CBP, 90% of patients had evidence of healing on 3-month MRI (continuity of the ACL). More ACL healing on 3-month MRI was associated with better outcomes. Longer-term follow-up and clinical trials are needed to inform clinical practice.
Medicaid expansion and racial disparity in timely multidisciplinary treatment in muscle invasive bladder cancer
Authors: Changchuan Jiang, Stuthi Perimbeti, Lei Deng, Jiazhang Xing, Gurkamal S Chatta, Xuesong Han, Dharmesh Gopalakrishnan
Journal: JNCI Journal of the National Cancer Institute (2023)

Multidisciplinary cancer care (neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy) is crucial for outcome of muscle-invasive bladder cancer (MIBC), a potentially curable illness. Medicaid expansion through Affordable Care Act (ACA) increased insurance coverage especially among patients of racial minorities. This study aims to investigate the association between Medicaid expansion and racial disparity in timely treatment in MIBC.This quasi-experimental study analyzed Black and White individuals aged 18-64 years with stage II and III bladder cancer treated with neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy from National Cancer Database 2008-2018. Primary outcome was timely treatment started within 45 days following cancer diagnosis. Racial disparity is the percentage-point difference between Black and White patients. Patients in expansion and nonexpansion states were compared using difference-in-differences and difference-in-difference-in-differences analyses, controlling for age, sex, area-level income, clinical stage, comorbidity, metropolitan status, treatment type, and year of diagnosis.The study included 4991 (92.3% White, n = 4605; 7.7% Black, n = 386) patients. Percentage of Black patients who received timely care increased following the ACA in Medicaid expansion states (54.5% pre-ACA vs 57.4% post-ACA) but decreased in nonexpansion states (69.9% pre-ACA vs 53.7% post-ACA). After adjusting covariates, Medicaid expansion was associated with a net 13.7 percentage-point reduction of Black-White patient disparity in timely receipt of MIBC treatment (95% confidence interval = 0.5% to 26.8%; P < .01).Medicaid expansion was associated with statically significant reduction in racial disparity between Black and White patients in timely multidisciplinary treatment for MIBC.
Help me find treatments and clinical trials
Authors: Lorna Pender
Journal: BMJ (2023)

Help me find treatments and clinical trialsLorna Pender shares her experience of discussing treatments for alopecia and how learning about clinical trials would have helped her Lorna PenderMy alopecia started when I was 8 years old, but in 2019 I noticed my hair falling out much more rapidly than before.I could no longer camouflage the hair loss.I also noticed that my eyebrows were gone, my eyelashes had fallen out, and I had lost all my body hair too.The scalp hair loss accelerated rapidly, and I sank into a deep depression, with suicidal thoughts.
Vaccination in the war in Ukraine
Authors: Nataliia Bushkovska
Journal: BMJ (2023)

Vaccination in the war in UkraineA year into the Russia invasion of Ukraine, vaccination-both routine and for covid-19-is one of the casualties.Nataliia Bushkovska meets the doctors trying increase uptake Nataliia Bushkovska freelance journalistIn Ukraine, vaccination has always been challenging.In 2016, the country had the lowest routine immunisation rate in the world, according to Unicef.
eTRANSAFE: data science to empower translational safety assessment
Authors: Ferran Sanz, François Pognan, Thomas Steger-Hartmann, Carlos Díaz, Shoji Asakura, Alexander Amberg, Nathalie Bécourt-Lhote, Niklas Blomberg, Nicolas Bosc, Katharine Briggs, Frank Bringezu, Claire Brulle-Wohlhueter, Søren Brunak, Ruud Bueters, Giulia Callegaro, Salvador Capella-Gutierrez, Emilio Centeno, Javier Corvi, Mark T. D. Cronin, Philip Drew, Guillemette Duchateau-Nguyen, Gerhard F. Ecker, Sylvia Escher, Eloy Felix, Miguel Ferreiro, Markus Frericks, Laura I. Furlong, Robert Geiger, Catherine George, Melanie Grandits, Dragomir Ivanov-Draganov, Jean Kilgour-Christie, Tevfik Kiziloren, Jan A. Kors, Naoki Koyama, Annika Kreuchwig, Andrew R. Leach, Miguel-Angel Mayer, Peter Monecke, Wolfgang Muster, Chihiro Miyamoto Nakazawa, Gavin Nicholson, Rowan Parry, Manuel Pastor, Janet Piñero, Nils Oberhauser, Juan Manuel Ramírez-Anguita, Adrián Rodrigo, Aljosa Smajic, Markus Schaefer, Sebastian Schieferdecker, Inari Soininen, Emma Terricabras, Panuwat Trairatphisan, Sean C. Turner, Alfonso Valencia, Bob van de Water, Johan L. van der Lei, Erik M. van Mulligen, Esther Vock, David Wilkinson
Journal: Nature Reviews Drug Discovery (2023)
Regulatory T cells in the face of the intestinal microbiota
Authors: Deepshika Ramanan, Alvin Pratama, Yangyang Zhu, Olivia Venezia, Martina Sassone-Corsi, Kaitavjeet Chowdhary, Silvia Galván-Peña, Esen Sefik, Chrysothemis Brown, Adélaïde Gélineau, Diane Mathis, Christophe Benoist
Journal: Nature reviews. Immunology (2023)
Detransition needs further understanding, not controversy
Authors: Kinnon Ross MacKinnon, Pablo Expósito-Campos, W Ariel Gould
Journal: BMJ (2023)

Kinnon MacKinnon and colleagues call for robust, sensitive research to inform comprehensive gender care services for people who detransition In recent years, public discourse has drawn attention to research and clinical practice regarding gender affirming care for transgender, non-binary, and gender diverse (trans) populations. In particular, the phenomenon of gender detransition—discontinuing or reversing gender affirming medical or surgical interventions—has been thrust into the spotlight through a highly publicised legal case in the UK, brought by someone who detransitioned, that challenges the ability of people younger than 16 years to give informed consent to start medical gender affirming treatment.1 At the same time politically driven efforts across the United States are seeking to restrict those under the age of 18 from receiving gender affirming care, citing that limited long term evidence contraindicates gender affirming care for children and adolescents.23 The flurry of media attention has highlighted the complexity underlying the science of gender care and the reality that, for some trans people, gender identity and care needs may change over time. Yet media stories about detransition often disproportionately feature those who want to limit access to treatments for gender dysphoria. Understanding the full range of experiences and perspectives of people who detransition—who may be referred to as detransitioners or detrans people—is crucial to advancing the field of gender care (box 1). Box 1 ### Glossary of key concepts relevant to research and practiceRETURN TO TEXT
Effectiveness of GRACE risk score in patients admitted to hospital with non-ST elevation acute coronary syndrome (UKGRIS): parallel group cluster randomised controlled trial
Authors: Chris P Gale, Deborah D Stocken, Suleman Aktaa, Catherine Reynolds, Rachael Gilberts, David Brieger, Kathryn Carruthers, Derek P Chew, Shaun G Goodman, Catherine Fernandez, Linda D Sharples, Andrew T Yan, Keith Fox
Journal: BMJ (2023)

Abstract Objective To determine the effectiveness of risk stratification using the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) for patients presenting to hospital with suspected non-ST elevation acute coronary syndrome. Design Parallel group cluster randomised controlled trial. Setting Patients presenting with suspected non-ST elevation acute coronary syndrome to 42 hospitals in England between 9 March 2017 and 30 December 2019. Participants Patients aged ≥18 years with a minimum follow-up of 12 months. Intervention Hospitals were randomised (1:1) to patient management by standard care or according to the GRS and associated guidelines. Main outcome measures Primary outcome measures were use of guideline recommended management and time to the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospital admission, and readmission for cardiovascular event. Secondary measures included the duration of hospital stay, EQ-5D-5L (five domain, five level version of the EuroQoL index), and the composite endpoint components. Results 3050 participants (1440 GRS, 1610 standard care) were recruited in 38 UK clusters (20 GRS, 18 standard care). The mean age was 65.7 years (standard deviation 12), 69% were male, and the mean baseline GRACE scores were 119.5 (standard deviation 31.4) and 125.7 (34.4) for GRS and standard care, respectively. The uptake of guideline recommended processes was 77.3% for GRS and 75.3% for standard care (odds ratio 1.16, 95% confidence interval 0.70 to 1.92, P=0.56). The time to the first composite cardiac event was not significantly improved by the GRS (hazard ratio 0.89, 95% confidence interval 0.68 to 1.16, P=0.37). Baseline adjusted EQ-5D-5L utility at 12 months (difference −0.01, 95% confidence interval −0.06 to 0.04) and the duration of hospital admission within 12 months (mean 11.2 days, standard deviation 18 days v 11.8 days, 19 days) were similar for GRS and standard care. Conclusions In adults presenting to hospital with suspected non-ST elevation acute coronary syndrome, the GRS did not improve adherence to guideline recommended management or reduce cardiovascular events at 12 months. Trial registration ISRCTN 29731761
Breathing difficulties after covid-19: a guide for primary care
Authors: Rachael Evans, Anton Pick, Rachel Lardner, Vicki Masey, Nikki Smith, Trisha Greenhalgh
Journal: BMJ (2023)

What you need to know• Breathing difficulties are common sequelae of covid-19 • Typically there are multiple contributing factors to breathing difficulties within an individual • Breathing pattern disorder can be positively diagnosed from the history and clinical examination, but parallel investigations to rule out other causes may be necessary • Self management support tools may help some patients regain a normal breathing pattern • Further investigation and specialist respiratory physiotherapy should be considered when symptoms are not improvingAround one in four adults who were hospitalised with covid-19 and one in six who were not hospitalised experience persistent breathing difficulties beyond four weeks after SARS-CoV-2 infection, 1 2 and a cohort study in China demonstrated that breathlessness can persist beyond two years. 3 In long covid (defined as symptoms beyond four weeks 4 ) breathing difficulties can be the predominant feature or be part of a multisystem presentation. 5Cardiorespiratory complications after covid-19 include thromboembolic disease, interstitial lung disease, and heart failure and need to be excluded.This article predominantly focuses on other, more common causes of post-covid breathing difficulties that can be treated but are often less well understood. 6finitive, evidence based protocols and treatment for persistent breathlessness after covid-19 are currently lacking.Until they exist, the pragmatic approach outlined here, including a careful history and examination and appropriate use of investigations, should help identify treatable conditions and improve symptoms.In particular, a positive diagnosis of breathing pattern disorder (box 2) can often be made in general practice.Self management resources (box 3) should be offered early.Timely referral to specialist services is needed for patients whose symptoms are severe or progressive. Presentation of breathing difficultiesBreathing difficulties can present in several ways, including breathlessness or pressure, tightness, soreness, and pain or burning in the chest.These symptoms can be associated with considerable distress.The general multisystem approach and investigation of breathlessness tends to be similar despite the interval between healthcare presentation and infection.Although there is some natural recovery in persisting symptoms between four to 12 weeks, it is difficult to predict at an individual level, and early support is often needed. 7Box 1 describes a typical patient narrative.
SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease
Authors: Hendrik Luxenburger, Robert Thimme
Journal: Gut (2023)

SARS-CoV-2 infection may affect the liver in healthy individuals but also influences the course of COVID-19 in patients with chronic liver disease (CLD). As described in healthy individuals, a strong SARS-CoV-2-specific adaptive immune response is important for the outcome of COVID-19, however, knowledge on the adaptive immune response in CLD is limited.Here, we review the clinical and immunological features of SARS-CoV-2 infection in individuals with CLD. Acute liver injury occurs in many cases of SARS-CoV-2 infection and may be induced by multiple factors, such as cytokines, direct viral infection or toxic effects of COVID-19 drugs. In individuals with CLD, SARS-CoV-2 infection may have a more severe course and promote decompensation and particularly in patients with cirrhosis. Compared with healthy individuals, the SARS-CoV-2-specific adaptive immune responses is impaired in patients with CLD after both, natural infection and vaccination but improves at least partially after booster vaccination.Following SARS-CoV-2 vaccination, rare cases of acute vaccine-induced liver injury and the development of autoimmune-like hepatitis have been reported. However, the concomitant elevation of liver enzymes is reversible under steroid treatment.
Deciphering the Heterogeneity Landscape of Mesenchymal Stem/Stromal Cell‐Derived Extracellular Vesicles for Precise Selection in Translational Medicine (Adv. Healthcare Mater. 15/2023)
Authors: Ye Li, Yin‐Hsueh Chen, Bing‐Yun Liu, Qing Nie, Li‐Jun Li, Xu Duan, Lian‐Zhi Wu, Gang Chen
Journal: Advanced Healthcare Materials (2023)

Extracellular Vesicles In article 2202453, Gang Chen and co-workers thoroughly decipher the heterogeneity landscape of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) through a combination of assessments from basic properties to translational potential, providing a precise strategy in the selection of MSC-EVs for the clinical utilization. The distinguishing therapeutic efficacy of MSC-EVs favored in various diseases of human organs resembles the abundant patterns of elements in the human body as a microcosm of nature.
Controlled Cascade‐Release and High Selective Sterilization by Core–Shell Nanogels for Microenvironment Regulation of Aerobic Vaginitis (Adv. Healthcare Mater. 15/2023)
Authors: Xinxin Wang, Yiting Wang, Mengteng Tang, Xiaoyi Wang, Wei Xue, Xiao Zhang, Yuxia Wang, Wen‐Hui Lee, Yingshuai Wang, Tong‐Yi Sun, Yuanyuan Gao, Li‐Li Li
Journal: Advanced Healthcare Materials (2023)

Aerobic Vaginitis Aerobic vaginitis is closely related to the imbalance of the vaginal microenvironment. In article 2202432 by Tong-Yi Sun, Yuanyuan Gao, Li-Li Li, and co-workers, a dynamically responsive core–shell nanogel (CSNG) is designed. CSNG can achieve a controlled temporal release of the antimicrobial peptide and prebiotic, which can achieve high selective sterilization of pathogenic bacteria and promote the growth of beneficial bacteria simultaneously.
Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion (Adv. Healthcare Mater. 15/2023)
Authors: Yanhao Li, Chengfang Hu, Bo Hu, Jian Tian, Gang Zhao, Chuandong Cai, Yuange Li, Zhenyu Sun, Shuo Wang, Sa Pang, Rong Bao, Zaijing Tao, Huajiang Chen, Jinglei Wu, Shen Liu
Journal: Advanced Healthcare Materials (2023)

Drug-Grafted Polymers In article 2203078 by Huajiang Chen, Jinglei Wu, Shen Liu, and co-workers, polylactic acid (PLA)-dicumarol conjugates are synthesized by grafting the hydroxyl of dicumarol to the carboxyl of PLA through esterification, and then electrospinning them into nanofiber membranes. Dicumarol releases in response to lipase to attenuate peritendinous adhesion formation by inhibiting Cx43/TGFβ1/Smad3 signaling pathway.
Selective Photothermal Therapy Based on Lipopolysaccharide Aptamer Functionalized MoS<sub>2</sub> Nanosheet‐Coated Gold Nanorods for Multidrug‐Resistant <i>Pseudomonas aeruginosa</i> Infection (Adv. Healthcare Mater. 15/2023)
Authors: Jie Lv, Bo Li, Tingting Luo, Chengtao Nie, Weilun Pan, Xiaoxue Ge, Jinsheng Zheng, Yongyu Rui, Lei Zheng
Journal: Advanced Healthcare Materials (2023)

Targeted Photothermal Therapy Combined with the outstanding photothermal conversion efficiency of gold nanorods (AuNRs), superior biocompatibility of molybdenum disulfide (MoS2) nanosheets, and strong specificity of lipopolysaccharides aptamer (LPS apt), composite nanorods (MoS2-AuNRs-apt) exhibit excellent therapeutic effects for multidrug-resistant pseudomonas aeruginosa and excess M1 macrophage in vitro, as well as infectious wounds in vivo. This work is found in article 2202794 by Yongyu Rui, Lei Zheng, and co-workers.
Visualization of nasal powder distribution using biomimetic human nasal cavity model
Authors: Jiawen Su, Yan Liu, Hongyu Sun, Abid Naeem, Huipeng Xu, Yue Qu, Caifen Wang, Zeru Li, Jianhua Lu, Lulu Wang, Xiaofeng Wang, Jie Wu, Lixin Sun, Jiwen Zhang, Zhigang Wang, Rui Yang, Li Wu
Journal: Acta Pharmaceutica Sinica B (2023)

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.